免疫反应及相关细胞因子在EV71相关手足口病合并肺水肿中的作用

摘要

目的:探讨细胞、体液免疫应答以及相关的细胞因子在EV71相关手足口病合并肺水肿中的作用.方法:将90例经鉴定为EV71感染患儿分为手足口病合并肺水肿组38例,手足口病无并发症组52例,并设查体健康对照组28例.ELISA法检测90例EV71感染引起的手足口病患儿血清IL-6、IL-10、TNF-α及IFN-γ含量;采用流式细胞仪对血液中CD3+T、CD4+及CD8+T细胞百分比进行检测;采用免疫比浊法对90例EV71感染引起的手足口病患儿血清免疫球蛋白(IgG、IgA及IgM)及补体C3、C4含量进行检测.结果:手足口病合并肺水肿组患儿血清IL-6、IL-10及IFN-γ含量明显升高,同时伴随CD4+及CD8+T细胞百分比下降;手足口病合并肺水肿组,无并发症组及健康对照组患儿血清IgM分别为1.85± 0.73,1.46±0.790和0.88± 0.39,三组之间差别具有统计学意义(F=14.967,P＜0.05).而IgG与IgA在三组之间无明显变化(X2=5.535,P＞0.05; F=1.988,P＞0.05);手足口病患儿血清C3及C4含量均明显低于健康对照组(F=46.079;62.794,P＜0.05).结论:由IL-10及IFN-γ的异常释放而引起的广泛的中枢及外周神经系统炎症反应和T淋巴细胞衰竭是引起EV71合并肺水肿病程进展的重要原因;在EV71感染后引发的手足口病进程中存在IgM的大量释放,且伴随补体C3、C4的消耗.%Objective: To determine the effect of cellullar immunologic response, humoral reactions and cytokine in children with pulmonary edema after enterovirus-71 -related hand, foot and mouth disease. Methods: Children who confirmed infected by enterovirus-71 were divided into two groups: 38 patients with pulmonary edema and 52 patients without complications. And 28 patients were considered as health control group. Serum IL-6, IL-10, TNF-α and IFN-γ were detected by ELISA. Flow cytometry was used to analyze the number of CD4+ and CD8+T cell in leukomonocyte suspension. And serum immunoglobin and complement (C3, C4) were detected by immunoturbidimetry. Results: A significant elevation of plasma interleukin (IL)-IO and interferon (IFN)-Y levels observed in patients with PE. Patients with PE also had lower circulating CD4+T cells and CD8+T cells. Serum IgM levels were 1.85± 0.73 and 1.46± 0.79 respectively in children in groups with complications and without complications, which significantly higher than that (0.88 ± 0.39) in patients in controls (F=6.287, P<0.05). However, The IgG and IgA levels have no significant changes among the three groups (X2 = 5.535, P>0.05; F =1.988, P>0.05). Compared with patients in health control group, patients who experienced enterovirus-71 had decreasing C3 levels. So were serum levels of C4 (F = 46.079; 62.794, P <0.05).Conclusion: An extensive central and peripheral nervous system inflammatory response with abnormal IL-10, and IFN-γ cytokine production and T lymphocyte decreasing appears to be responsible for the pathogenesis of EV71 -associated PE. There have excessive immunoglobin production of IgM with decreasing C3 and C4 in patients with PE.